Wound care procedures, such as dressing changes, cause moderate to severe pain in 74% of patients, nearly half (36%) of whom experience severe pain (rated as 8 to 10 on a 10-point numeric rating scale). Severe pain causes substantial stress for both patient and nurse. Unfortunately, the high prevalence of severe pain during WCPs is under-recognized and under-studied. To date, mainstay recommendations to prevent pain during WCPs have focused on either administration of preventive and procedural analgesia or use of expensive, non-adherent dressings. However, it is unclear which patients to target for analgesia or expensive dressings, leading to their inappropriate over or under use. Analgesics are given to only 23% of patients undergoing WCPs and dressings that may decrease pain are given to even fewer. The ability to predict which patients are likely to have severe pain during WCPs is critically needed so that they can be targeted for preventive pain control strategies, including use of opioid analgesics and special dressings. Aim 1 of this study is to develop and evaluate a model to predict severe pain during WCPs. Although opioids are often given for highly painful conditions, they may not be an optimal or adequate strategy for controlling pain in open wounds because they impair wound healing and could lead to wound chronicity. The arsenal of alternatives to opioids is extremely limited because the biological mechanisms that contribute to nociceptive sensitivity and high pain during WCPs are unknown. Knowledge of these mechanisms would direct the development of new, effective interventions. Aim 2 is to identify these mechanisms. We have assembled an exceptional multi-disciplinary team of investigators to execute the aims of this proposal. These include investigators with expertise in: clinical research of chronic wounds (PI: Gardner), clinical (Investigator: Rakel) and basic science (Consultant: Brennan) research of pain, genomic technologies to measure wound bioburden (Investigator: Grice), and statistical analyses, including receiver operating curves (Statistician: Hillis). To achieve the aims of the study, a comprehensive set of wound, patient, and biological factors will be measured concurrently with pain during a dressing change among a sample of 450 inpatients with open wounds. A predictive model will be developed and biological mechanisms will be examined using logistic regression. The model will be evaluated using receiver operator characteristic curves. The proposed study has the potential to make significant contributions because clinicians will be able to target those patients requiring preventive pain control, thereby eliminating the spiraling impact of painful procedures on nociceptor sensitization. In addition, the findings will provide foundational evidence for the development of needed, novel pain control strategies. The positive impact will be to optimize wound care, minimize adverse effects of pain and treatment, and reduce the costs associated with wound care.